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Heterozygous Mutations in OAS1 Cause Infantile-Onset Pulmonary Alveolar Proteinosis with Hypogammaglobulinemia

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Title: Heterozygous Mutations in OAS1 Cause Infantile-Onset Pulmonary Alveolar Proteinosis with Hypogammaglobulinemia
Authors: Cho, Kazutoshi Browse this author →KAKEN DB
Yamada, Masafumi Browse this author
Agematsu, Kazunaga Browse this author
Kanegane, Hirokazu Browse this author
Miyake, Noriko Browse this author
Ueki, Masahiro Browse this author
Akimoto, Takuma Browse this author
Kobayashi, Norimoto Browse this author
Ikemoto, Satoru Browse this author
Tanino, Mishie Browse this author →KAKEN DB
Fujita, Atsushi Browse this author
Hayasaka, Itaru Browse this author
Miyamoto, Satoshi Browse this author
Tanaka-Kubota, Mari Browse this author
Nakata, Koh Browse this author
Shiina, Masaaki Browse this author
Ogata, Kazuhiro Browse this author
Minakami, Hisanori Browse this author →KAKEN DB
Matsumoto, Naomichi Browse this author
Ariga, Tadashi Browse this author →KAKEN DB
Keywords: 2',5'-oligoadenylate synthetase 1
OAS1
pulmonary alveolar proteinosis
PAP
hypogammaglobulinemia
alveolar macrophage
Issue Date: 1-Mar-2018
Publisher: Cell Press
Journal Title: The American Journal of Human Genetics
Volume: 102
Issue: 3
Start Page: 480
End Page: 486
Publisher DOI: 10.1016/j.ajhg.2018.01.019
Abstract: Pulmonary alveolar proteinosis (PAP) is characterized by accumulation of a surfactant-like substance in alveolar spaces and hypoxemic respiratory failure. Genetic PAP (GPAP) is caused by mutations in genes encoding surfactant proteins or genes encoding a surfactant phospholipid transporter in alveolar type II epithelial cells. GPAP is also caused by mutations in genes whose products are implicated in surfactant catabolism in alveolar macrophages (AMs). We performed whole-exome sequence analysis in a family affected by infantile-onset PAP with hypogammaglobulinemia without causative mutations in genes associated with PAP: SFTPB, SFTPC, ABCA3, CSF2RA, CSF2RB, and GATA2. We identified a heterozygous missense variation in OAS1, encoding 2',5'-oligoadenylate synthetase 1 (OAS1) in three affected siblings, but not in unaffected family members. Deep sequence analysis with next-generation sequencing indicated 3.81% mosaicism of this variant in DNA from their mother's peripheral blood leukocytes, suggesting that PAP observed in this family could be inherited as an autosomal-dominant trait from the mother. We identified two additional de novo heterozygous missense variations of OAS1 in two unrelated simplex individuals also manifesting infantile-onset PAP with hypogammaglobulinemia. PAP in the two simplex individuals resolved after hematopoietic stem cell transplantation, indicating that OAS1 dysfunction is associated with impaired surfactant catabolism due to the defects in AMs.
Rights: © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
http://creativecommons.org/licenses/by-nc-nd/4.0/
Type: article (author version)
URI: http://hdl.handle.net/2115/71413
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 長 和俊

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